PB2551: GAUCHER DISEASE CURRICULUM: INCORPORATING GAUCHER DISEASE IN THE FIELD OF HEMATOLOGY
Authors: Argiris Symeonidis, Colm Bradley, Sam Salek
Journal: HemaSphere (2023)

Topic: 28. Enzymopathies, membranopathies and other anemias Background: Gaucher Disease (GD) is an inherited Lysosomal Storage Disorder, resulting from mutations of the glucocerebosidase (GCase) gene and characterized by accumulation of undigested glucosylceramide in macrophages. It is presented with organomegaly, blood cytopenias, coagulation abnormalities and osteolytic bone disease, mimicking multiple myeloma. Patients have deranged immunological profile and an increased risk for development of hematological malignancies, particularly myeloma. There is a strong hematological component and a strong involvement of hematologists in the management of GD. However, GD has not yet been considered part of education for the trainees in Hematology. Aims: To create and propose a curriculum for GD, which should be adopted as part of the educational training in Hematology in Europe. Methods: GD is already mentioned in the 1-Ο section of the Hematology passport of EHA. We herein describe what the knowledge about GD of a trainee hematologist should include. This is an activity of the GD Task Force, an independent SubCommittee of the Granulocytes and Constitutional Marrow Failure Syndromes’ Scientific Working Group of EHA. Results: GD should be included in the differential diagnosis of splenomegaly, chronic thrombocytopenia, chronic inflammatory reaction, unexplained coagulation abnormalities and of skeletal bone disease. All graduates in hematology should know sphingolipid biochemistry, GCase gene structure, its more common pathogenetic mutations leading to GD, the clinical severity of each of them, and the role of sapocin-C. They should also know the structure of normal and of sphingolipid-filled lysosomes, normal glucosphingolipid metabolism and its derangement in GD, basic elements of disease epidemiology, mode of inheritance and ethnic distribution. Further, they should know the 3 subtypes of GD, their basic clinical manifestations and complications, the characteristic radiological signs of bone involvement and painful crises, the main neurological manifestations, including the pathognomonic saccadic eye movements of neuronopathic subtypes and the association of GD with Parkinson’s disease. They should also know the less common clinical manifestations and complications, such as interstitial pneumonopathy, cardiac valve and coronary vessel involvement, cataract, and the pseudo-tumorous gaucheromas. All hematologists should be capable to perform a complete diagnostic process for GD, without a bone marrow examination and they should know the two major types of treatment, namely Enzyme Replacement Treatment (ERT) and Substrate Reduction Treatment (SRT), the available drugs and treatment monitoring. They should be aware of the prenatal diagnosis as well as genetic counseling for primary prevention. Finally, all hematologists should be aware of lipid signaling in neoplastic disorders, the association of GD with hematological malignancies and particularly with monoclonal gammopathy of Undetermined Significance and multiple myeloma and apply periodical relevant screening for these potential risks to their patients. Summary/Conclusion: GD curriculum should be included in the main body of education in Hematology, and Hematology departments should allow trainees and young hematologists to visit expert GD centers for short periods of time, to obtain experience of this disease. We recommend adoption of GD curriculum by the EHA and its inclusion as one of the masterclasses, as part of harmonizing training for early career hematologists, promoted by both, H-net and CVP, hoping that it will be considered by the European Board for Accreditation in Hematology (EBAH). Keywords: Gaucher disease